Treatment completion rate [ Time Frame: From the date of randomization to the date when patients complete consolidation chemotherapy or have a cyctectome with four cycles of gemcitabine and cisplatin. ] [ Designated as safety issue: No ]

Grade 3 or more genitourinary, gastrointestinal, and hematologic toxicities as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 [ Time Frame: Acute toxicities - From treatment start date to the end of treatment. Late adverse events - 180 days from the end of treatment. ] [ Designated as safety issue: Yes ]

Complete response of the primary tumor [ Time Frame: Three to four weeks from completion of induction chemotherapy. ] [ Designated as safety issue: No ]

Preservation of the native, tumor-free bladder 5 years after completion of study therapy [ Time Frame: Five years from the date of trasurethral surgery. ] [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery.

Detailed Description

OBJECTIVES:

Primary

To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin.

Secondary

To estimate the treatment completion rate in these patients.

To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients.

To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients.

To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients.

To find potentially predictive biomarkers for acute and late toxicities.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.

Induction therapy (weeks 1-4):

Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 15-17 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also undergo radiotherapy twice daily on days 1-5, 8-12, and 15-17.

All patients undergo evaluation of response at 3-4 weeks after completion of induction therapy. Patients with pT1 or worse tumor response undergo radical cystectomy within 3-8 weeks after response evaluation. Patients with pT0, Ta, or Tis tumor response (at site distant from original tumor) proceed to consolidation therapy within 7-14 days after response evaluation.

Consolidation therapy (weeks 8-10):

Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 8-10 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also undergo radiotherapy twice daily on days 1-5 and 8-10.

Adjuvant therapy (weeks 21-33 or 17-29): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.